Effectiveness of donepezil, rivastigmine and ({+/-})huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: Comparison with galantamine. The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] Journal article | | Title | Effectiveness of donepezil, rivastigmine and ({+/-})huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: Comparison with galantamine. | | Author(s) | Aracava Y, Pereira E, Akkerman M, Adler M, Albuquerque EX | | Institution | Univ Maryland Sch Med. | | Source | J Pharmacol Exp Ther 2009 Sep 9. | | Abstract | Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared to that of the centrally active ChE inhibitors donepezil, rivastigmine and (+/-)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5xLD50 soman (42 microg/kg, sc). All animals that were pre-treated with galantamine (6-8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine or 0.3 mg/kg (+/-)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg, im). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine or 0.3 mg/kg (+/-)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pre-treatment in animals challenged with 1.0xLD50 soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0xLD50 soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 and 3 h after the challenge with 0.6x or 0.7xLD50 soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19741148 |
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